Summary

Name:

680: Solo Hand-Folding Sepsis Puzzle

Status:

Closed

Created:

02/26/2013

Points:

100

Expired:

03/09/2013 - 16:00

Difficulty:

Intermediate

Description:

Sugar molecules such as the one here are coated on the surface of many human pathogens. We are attempting to increase the protein-sugar binding interactions by allowing you to redesign & insert up to 10 residues to form additional hydrogen bonds with the sugar. To encourage this, only GUI scripts are allowed, and sharing has been disabled. After this puzzle expires, the puzzle will be re-posted and LUA scripts and sharing will be allowed. You will be able to load in your solutions from the first puzzle and refine them with scripting and sharing. Please read the new blogpost & puzzle comments for more details.

We realize that not everyone loves Hand-Folding puzzles, but don't worry:
the "normal" version of this puzzle will be reposted next week (allowing you to you to load in your manual saves from this puzzle).

The motivation for making the initial round of this Sepsis Design Puzzle "Hand-Folding only" is because the goal is this puzzle is to increase the number and strength of protein-sugar interactions. This is very hard to do with scripts, so we'd really like you to focus on trying to do that manually.

We have unlocked GUI scripts, not because we want you to heavily use & rely on them, but so that simple things like shaking/wiggling don't have to be manually done all the time.

Sharing has also been disabled for this round, as we want to try to get as many diverse solutions as possible before players start evolving their teammate's solutions.

We know this puzzle will require a larger time investment than usual (which is why it is up for over 10 days) but hopefully the goal of this puzzle will make that time investment worthwhile.

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If you are new to Foldit, make sure you have completed Intro Puzzles 7-1 through 7-4 before trying this puzzle.
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This puzzle has the ResidueIE filter on (to ensure PHE, TYR, and TRP residues are scoring properly) and we've increased the Ligand Score by a factor of 10 to promote interactions with the sugar.

Tip: To see the parts of the sugar that you can bond to, check Show bonds (non-protein) and Show bondable atoms in the View menu. Make sure Show bonds (loop) and Show bonds (sidechain) are also on. Blue can bond to red, and purple can bond to either blue or red.
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Crash Warning: Do not enable the 'Show Isosurface' view option, as it will crash with this puzzle. We hope to fix this soon!

I have reworded this sentence so that it reads "to ensure PHE, TYR, and TRP residues are scoring properly".

The main purpose of the residueIE filter is to prevent unrealistic residue substitutions in Foldit.
For example, it makes adding tryptophans, tyrosines, and phenylalanines on the surface of a protein score poorly. Putting hydrophobic residues on the surface is bad because it makes the protein very "sticky", likely to interact with many other proteins, including itself, and hence not very useful.

So when I said we want them to score "well", I meant that they should only get a high Foldit score if they are in the proper location in the protein (most likely buried in the core of the protein), as we want your designs to be as useful as possible, since the problem we are trying to solve with this protein is already hard enough!

But still i'm wondering whether it works like you wrote. When I have a PHE buried deep in the protein near the ligand and no exposed is showing I assume it should not be penalized by the filter then. But still it does, so.....! Or is it maybe that there are very specific places where it scores well? but that would be strange because then you apparently know where they should come. Puzzling:-)

I think you haven't seen my question about the placement of PHE, TYR and TRP in relation to the filter^^

""Hi Beta, thanks for the quick response.

But still i'm wondering whether it works like you wrote. When I have a PHE buried deep in the protein near the ligand and no exposed is showing I assume it should not be penalized by the filter then. But still it does, so.....! Or is it maybe that there are very specific places where it scores well? but that would be strange because then you apparently know where they should come. Puzzling:-)""

Could you do a couple things to help us figure out exactly what's going on here?

1) Save your solution and tell us the name of the save
2) If you are using devprev, press TAB on the residue in question and scroll down past all of the energy values. You should see "ResidueIE Filter:" and then a line giving you the "Interaction Energy" and "Required". Tell us what those values are. If you are not using devprev, the change that adds this data should be going out to main later today

I pulled out the ligand to find out if the ligand would cause the IE to change. It does, but only negatively. With the ligand completely removed, the IE is basically the same as when it is there.

I then replaced the ligand with some ALA to test out if it was a difference between ligands and normal aa. The buried TYR still scored poorly. So it looks like it's just a function of the interaction energy and positioning itself, not an issue with it being a ligand.

Tip: To see the parts of the sugar that you can bond to, check Show bonds (non-protein) and Show bondable atoms in the View menu. Make sure Show bonds (loop) and Show bonds (sidechain) are also on. Blue can bond to red, and purple can bond to either blue or red.